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Nat Rev Nephrol. 2016 May;12(5):281-90. doi: 10.1038/nrneph.2016.41. Epub 2016 Mar 30.

Role of TLRs and DAMPs in allograft inflammation and transplant outcomes.

Author information

1
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 2780-156 Oeiras, Portugal.
2
INSERM, UMR 1064, CHU de Nantes, ITUN, 30 Bd Jean Monnet Nantes F-44093, France.
3
Renal Medicine and Transplantation, Royal Prince Alfred Hospital, Missenden Road Camperdown, NSW 2050, Sydney, Australia.
4
Kidney Node, Charles Perkins Centre, University of Sydney, Missenden Road, Camperdown, NSW 2093, Australia.
5
Department of Internal Medicine, 333 Cedar St, Yale School of Medicine, New Haven, Connecticut 06525, USA.
6
Department of Immunobiology, 300 Cedar St, Yale School of Medicine, New Haven, Connecticut 06525, USA.

Abstract

Graft inflammation impairs the induction of solid organ transplant tolerance and enhances acute and chronic rejection. Elucidating the mechanisms by which inflammation is induced after organ transplantation could lead to novel therapeutics to improve transplant outcomes. In this Review we describe endogenous substances--damage-associated molecular patterns (DAMPs)--that are released after allograft reperfusion and induce inflammation. We also describe innate immune signalling pathways that are activated after solid organ transplantation, with a focus on Toll-like receptors (TLRs) and their signal adaptor, MYD88. Experimental and clinical studies have yielded a large body of evidence that TLRs and MYD88 are instrumental in initiating allograft inflammation and promoting the development of acute and chronic rejection. Ongoing clinical studies are testing TLR inhibition strategies in solid organ transplantation, although avoiding compromising host defence to pathogens is a key challenge. Further elucidation of the mechanisms by which sterile inflammation is induced, maintained and amplified within the allograft has the potential to lead to novel anti-inflammatory treatments that could improve outcomes for solid organ transplant recipients.

PMID:
27026348
DOI:
10.1038/nrneph.2016.41
[Indexed for MEDLINE]

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